MUC1 is a member of the mucin protein family, which is over-expressed in tumor cells and surrounds all surfaces of the tumor cells, as a significant symbol of tumor. The mucin MUC1 is an attractive target for the development of an immunotherapy against cancer. Its extracellular domain contains numerous tandem repeats of the sequence, which includes five potential glycosylation sites.MUC1 is weak immunogenic, since it is a self-antigen. Therefore, how to increase the immunogenicity is significant. To overcome the poor immunogenicity of MUC1, many strategies are employed today including combination with carrier proteins, peptide templates, nanoparticles and other adjuvants.For a novel design of chemical tumor vaccine, we constructed several totally synthetic vaccine candidates with self-assembly domain Q11 and B-cell epitopes[1]. After self-assembling in neutral condition, the vaccine candidates formed fibers and elicited immune response without adjuvant. The fibrillar structure could display multivalent B-cell epitopes under mild condition. The PDTRP sequence with Tn antigen modification on Thr residue could induce an effective immune response. The high titer of the antibody in response to the adjuvant-free vaccine and the recognition of the antibody to human breast tumor cells proved that the vaccines have good immune effect. A T-cell independent pathway and the activation of cytotoxic T cells were detected after immunization. Therefore, the totally synthetic, self-assembling, adjuvant-free MUC1 glycopeptide vaccine was a promising approach for anticancer therapy.References[1] Huang, Z. H.; Shi, L.; Ma, J. W.; Sun, Z. Y.; Cai, H.; Chen, Y. X.; Zhao, Y. F.; Li, Y. M. J. Am. Chem. Soc.2012, 134, 8730-8733.

Self-assembling MUC1 glycopeptide vaccine for cancer therapy

248th National Meeting (2014)

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